Interspecies chimerism with human embryonic stem cells generates functional human dopamine neurons at low efficiency.

ABSTRACT: Interspecies chimeras offer great potential for regenerative medicine and the creation of human disease models. Whether human pluripotent stem cell-derived neurons in an interspecies chimera can differentiate into functional neurons and integrate into host neural circuity is not known. Here, we show, using Engrailed 1 (En1) as a development niche, that human naive-like embryonic stem cells (ESCs) can incorporate into embryonic and adult mouse brains. Human-derived neurons including tyrosine hydroxylase (TH)⁺ neurons integrate into the mouse brain at low efficiency. These TH⁺ neurons have electrophysiologic properties consistent with their human origin. In addition, these human-derived neurons in the mouse brain accumulate pathologic phosphorylated α-synuclein in respo

SUBMITTER: Wang H 

PROVIDER: S-EPMC10828682 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature